Physical properties of biological entities: an introduction to the ontology of physics for biology

As biomedical investigators strive to integrate data and analyses across spatiotemporal scales and biomedical domains, they have recognized the benefits of formalizing languages and terminologies via computational ontologies. Although ontologies for biological entities-molecules, cells, organs-are well-established, there are no principled ontologies of physical properties-energies, volumes, flow rates-of those entities. In this paper, we introduce the Ontology of Physics for Biology (OPB), a reference ontology of classical physics designed for annotating biophysical content of growing repositories of biomedical datasets and analytical models. The OPB's semantic framework, traceable to James Clerk Maxwell, encompasses modern theories of system dynamics and thermodynamics, and is implemented as a computational ontology that references available upper ontologies. In this paper we focus on the OPB classes that are designed for annotating physical properties encoded in biomedical datasets and computational models, and we discuss how the OPB framework will facilitate biomedical knowledge integration.     

Sexual dimorphism of the human mandible and its association with dental development

The present study investigates whether the human mandible is sexually dimorphic during early postnatal development and whether early dimorphic features persist during subsequent ontogeny. We also examine whether mandibular dimorphism is linked to dimorphism of dental development. Dense CT-derived mandibular meshes of 84 females and 75 males, ranging from birth to adulthood, were analyzed using geometric morphometric methods. On the basis of the specimen's chronological ages and mineralization stages of the deciduous and permanent teeth, we compute dental age as proxy for dental development by the additive conjoint measurement method. By birth, males have, on average, more advanced age-specific shapes than females. However, sex differences decrease quickly as females catch up via a different association between shape and size. This leads to an almost complete reduction of sexual dimorphism between the ages of 4 and 14. From puberty to adulthood, males are characterized by allometric shape changes while the shape of the female mandible continues to change even after size has ceased to increase. Dimorphism of dental maturation becomes visible only at puberty. Sexual dimorphism, concentrated at the ramus and the mental region during the earliest ontogenetic stages and again at adulthood, is not associated with the development of the teeth. At puberty there is a simultaneous peak in size increase, shape development, and dental maturation likely controlled by the surge of sex hormones with a dimorphic onset age. We argue that the infant and adult dimorphism of the mental region may be associated with the development of supralaryngeal structures.     

Structure of the Pseudorabies Virus Capsid: Comparison with Herpes Simplex Virus Type 1 and Differential Binding of Essential Minor Proteins

The structure of pseudorabies virus (PRV) capsids isolated from the nucleus of infected cells and from PRV virions was determined by cryo-electron microscopy (cryo-EM) and compared to herpes simplex virus type 1 (HSV-1) capsids. PRV capsid structures closely resemble those of HSV-1, including distribution of the capsid vertex specific component (CVSC) of HSV-1, which is a heterodimer of the pUL17 and pUL25 proteins. Occupancy of CVSC on all PRV capsids is near 100%, compared to ~ 50% reported for HSV-1 C-capsids and 25% or less that we measure for HSV-1 A- and B-capsids. A PRV mutant lacking pUL25 does not produce C-capsids and lacks visible CVSC density in the cryo-EM-based reconstruction. A reconstruction of PRV capsids in which green fluorescent protein was fused within the N-terminus of pUL25 confirmed previous studies with a similar HSV-1 capsid mutant localizing pUL25 to the CVSC density region that is distal to the penton. However, comparison of the CVSC density in a 9-Å-resolution PRV C-capsid map with the available crystal structure of HSV-1 pUL25 failed to find a satisfactory fit, suggesting either a different fold for PRV pUL25 or a capsid-bound conformation for pUL25 that does not match the X-ray model determined from protein crystallized in solution. The PRV capsid imaged within virions closely resembles C-capsids with the addition of weak but significant density shrouding the pentons that we attribute to tegument proteins. Our results demonstrate significant structure conservation between the PRV and HSV capsids.     

WPA guidance on how to combat stigmatization of psychiatry and psychiatrists

In 2009 the WPA President established a Task Force that was to examine available evidence about the stigmatization of psychiatry and psychiatrists and to make recommendations about action that national psychiatric societies and psychiatrists as professionals could do to reduce or prevent the stigmatization of their discipline as well as to prevent its nefarious consequences. This paper presents a summary of the Task Force’s findings and recommendations. The Task Force reviewed the literature concerning the image of psychiatry and psychiatrists in the media and the opinions about psychiatry and psychiatrists of the general public, of students of medicine, of health professionals other than psychiatrists and of persons with mental illness and their families. It also reviewed the evidence about the interventions that have been undertaken to combat stigma and consequent discrimination and made a series of recommendations to the national psychiatric societies and to individual psychiatrists. The Task Force laid emphasis on the formulation of best practices of psychiatry and their application in health services and on the revision of curricula for the training of health personnel. It also recommended that national psychiatric societies establish links with other professional associations, with organizations of patients and their relatives and with the media in order to approach the problems of stigma on a broad front. The Task Force also underlined the role that psychiatrists can play in the prevention of stigmatization of psychiatry, stressing the need to develop a respectful relationship with patients, to strictly observe ethical rules in the practice of psychiatry and to maintain professional competence.     

Identification of multiple integrin β1 homologs in zebrafish (Danio rerio)

Background  

Integrins comprise a large family of α,β heterodimeric, transmembrane cell adhesion receptors that mediate diverse essential biological functions. Higher vertebrates possess a single β1 gene, and the β1 subunit associates with a large number of α subunits to form the major class of extracellular matrix (ECM) receptors. Despite the fact that the zebrafish (Danio rerio) is a rapidly emerging model organism of choice for developmental biology and for models of human disease, little is currently known about β1 integrin sequences and functions in this organism.     

Global assessment of nitrogen fertilizer: The SCOPE/IGBP Nitrogen Fertilizer Rapid Assessment Project

Nitrogen (N) availability is a key role in food and fiber production. Providing plant-available N through synthetic fertilizer in the 20th and early 21st century has been a major contributor to the increased production required to feed and clothe the growing human population. To continue to meet the global demands and to minimize environmental problems, significant improvements are needed in the efficiency with which fertilizer N is utilized within production systems. There are still major uncertainties regarding the fate of fertilizer N added to agricultural soils and the potential for reducing losses to the environment. Enhancing the technical and economic efficiency of fertilizer N is seen to promote a favorable situation for both agricultural production and the environment, and this has provided much of the impetus for a new N fertilizer project. To address this important issue, a rapid assessment project on N fertilizer (NFRAP) was conducted by SCOPE (the Scientific Committee on Problems of the Environment) during late 2003 and early 2004. This was the first formal project of the International Nitrogen Initiative (INI). As part of this assessment, a successful international workshop was held in Kampala, Uganda on 12 - 16 January, 2004. This workshop brought together scientists from around the world to assess the fate of synthetic fertilizer N in the context of overall N inputs to agricultural systems, with a view to enhancing the efficiency of N use and reducing negative impacts on the environment. Regionalization of the assessment highlighted the problems of too little N for crop production to meet the nutrient requirements of sub-Saharan Africa and the oversupply of N in the major rice-growing areas of China. The results of the assessment are presented in a book (SCOPE 65) which is now available to provide a basis for further discussions on N fertilizer.     

The tumor suppressor PTEN negatively regulates insulin signaling in 3T3-L1 adipocytes

PTEN is a tumor suppressor with sequence homology to protein-tyrosine phosphatases and the cytoskeleton protein tensin. PTEN is capable of dephosphorylating phosphatidylinositol 3,4, 5-trisphosphate in vitro and down-regulating its levels in insulin-stimulated 293 cells. To study the role of PTEN in insulin signaling, we overexpressed PTEN in 3T3-L1 adipocytes approximately 30-fold above uninfected or control virus (green fluorescent protein)-infected cells, using an adenovirus gene transfer system. PTEN overexpression inhibited insulin-induced 2-deoxy-glucose uptake by 36%, GLUT4 translocation by 35%, and membrane ruffling by 50%, all of which are phosphatidylinositol 3-kinase-dependent processes, compared with uninfected cells or cells infected with control virus. Microinjection of an anti-PTEN antibody increased basal and insulin stimulated GLUT4 translocation, suggesting that inhibition of endogenous PTEN function led to an increase in intracellular phosphatidylinositol 3,4,5-trisphosphate levels, which stimulates GLUT4 translocation. Further, insulin-induced phosphorylation of downstream targets Akt and p70S6 kinase were also inhibited significantly by overexpression of PTEN, whereas tyrosine phosphorylation of the insulin receptor and IRS-1 or the phosphorylation of mitogen-activated protein kinase were not affected, suggesting that the Ras/mitogen-activated protein kinase pathway remains fully functional. Thus, we conclude that PTEN may regulate phosphatidylinositol 3-kinase-dependent insulin signaling pathways in 3T3-L1 adipocytes.     

A PATH-ANALYTIC MODEL FOR THE MEASUREMENT OF SELECTION ON MORPHOLOGY

This paper describes a path model for the analysis of phenotypic selection upon continuous morphological characters. The path-analysis model assumes that selection occurs on unmeasured general size and shape allometry factors that summarize linear relations among sets of ontogenetically, phylogenetically, or functionally related traits. An unmeasured factor for general size is considered the only aspect of morphometric covariance matrices for which there is an a priori biological explanation. Consequently, selection coefficients are derived for each measured character by holding constant only a general size factor, rather than by using multiple regression to adjust for the full covariance matrix. Fitness is treated as an unmeasured factor with loadings, representing directional selection coefficients, computed as the covariances of the size-adjusted characters with the measured fitness indicator. The magnitudes and signs of the selection coefficients, combined with biological insight, may suggest hypotheses of selection on one or more shape allometry factors. Hypotheses of selection on general size and shape allometry factors are evaluated through cycles of measurement, analysis, and experimentation, designed to refine the path diagram depicting the covariances among the measured characters, the measured indicator of fitness, and unmeasured factors for morphology and fitness. The path-analysis and multiple-regression models were applied to data from remeasurement of Lande and Arnold's (1983) pentatomid bugs and to Bumpus's (1899) data on house sparrows. The path analysis suggested the hypothesis that variation in bug survivorship was an expression of directional selection on wing loading. Bumpus's data are consistent with a hypothesis of stabilizing selection on general size in females and directional selection for small wing size relative to body size in males.     

Tissue distribution of Na+/H+ exchanger isoforms NHE2 and NHE4 in rat intestine and kidney

We present evidence that tissue distribution of two highlyconservedNa⁺/H⁺exchanger isoforms, NHE2 and NHE4, differs significantly from previously published reports. Riboprobes unique to each of these antiporters, from 5' (noncoding and coding) and 3' codingregions, were used to analyze mRNA from adult rat kidney and intestine by ribonuclease protection assay and in situ hybridization. In contrastto earlier work that concluded that both NHE2 and NHE4 were expressedthroughout the intestine and in the kidney, our data show that there isno NHE2 message in the kidney and NHE4 is not expressed in small orlarge intestine. Analyses of intestinal epithelial and kidney membraneproteins by an NHE2-specific antibody identified a doublet at <90 kDain intestine but not in kidney. NHE2 is highly expressed in theNa⁺-absorptive epithelium ofjejunum, ileum, and ascending and descending colon. NHE4 mRNA messageis found in the inner medulla of the kidney as previously reported (C. Bookstein, M. W. Musch, A. DePaoli, Y. Xie, M. Villereal, M. C. Rao,and E. B. Chang. J. Biol. Chem. 269:29704-29709, 1994) and not in the intestine. From these data, wespeculate that neither NHE2 nor NHE4 has a role in renalNa⁺ absorption. NHE2 is likelyinvolved in gut Na⁺ absorption,whereas NHE4 may have a specialized role in cell volume rectificationof inner medullary collecting duct cells. Knowledge of the correcttissue and cell-specific distribution of these two antiporters shouldhelp significantly in understanding their physiological roles.